Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2.

Journal article

The LOX-1 scavenger receptor recognises pro-atherogenic oxidised low-density lipoprotein (OxLDL) particles and is implicated in atherosclerotic plaque formation, but this mechanism is not well understood. Here we show evidence for a novel clathrin-independent and cytosolic-signal-dependent pathway that regulates LOX-1-mediated OxLDL internalisation. Cell surface labelling in the absence or presence of OxLDL ligand showed that LOX-1 is constitutively internalised from the plasma membrane and its half-life is not altered upon ligand binding and trafficking. We show that LOX-1-mediated OxLDL uptake is disrupted by overexpression of dominant-negative dynamin-2 but unaffected by CHC17 or mu2 (AP2) depletion. Site-directed mutagenesis revealed a conserved and novel cytoplasmic tripeptide motif (DDL) that regulates LOX-1-mediated endocytosis of OxLDL. Taken together, these findings indicate that LOX-1 is internalised by a clathrin-independent and dynamin-2-dependent pathway and is thus likely to mediate OxLDL trafficking in vascular tissues.

Authors: Murphy, J; Vohra, R; Dunn, S; Holloway, Z; Monaco, A

• Publication status: Published
• Journal: Journal of cell science
• Volume: 121
• Issue: Pt 13
• Pages: 2136-2147
• Publication date: 2008-07-01
• DOI: 10.1242/jcs.020917
• EISSN: 1477-9137
• ISSN: 0021-9533
• Language: English
• Keywords: Mutagenesis, Site-Directed; Endocytosis; Signal Transduction; Lipoproteins, LDL; Humans; Protein Structure, Tertiary; Hela Cells; Scavenger Receptors, Class E; Amino Acid Motifs; Dynamin II; Protein Transport; Amino Acid Sequence; Protein Binding; Molecular Sequence Data